Treatment of Diabetic Neuropathy with A Novel PAR1-Targeting Molecule

Autor:	Valery Golderman, Yotam Teldan, Joab Chapman, Shany Guly Gofrit, Eiman Abu Bandora, Sagi Harnof, Ariel Ron, Efrat Shavit-Stein, Orna Gera, Amir Dori, Alexandra Gayster
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	Blood Glucose Male medicine.medical_specialty Diabetic neuropathy peripheral neuropathy Biochemistry streptozotocin Nerve conduction velocity Article Diabetes Mellitus Experimental 03 medical and health sciences Mice 0302 clinical medicine Thrombin Drug Delivery Systems Diabetic Neuropathies Diabetes mellitus Internal medicine medicine Animals Receptor PAR-1 Molecular Biology Hypoalgesia business.industry medicine.disease Streptozotocin thrombin PAR1 Peptide Fragments Mice Inbred C57BL Peripheral neuropathy Endocrinology Coagulation 030220 oncology & carcinogenesis diabetes mellitus cardiovascular system business 030217 neurology & neurosurgery medicine.drug
Zdroj:	Biomolecules Volume 10 Issue 11
ISSN:	2218-273X
Popis:	Diabetic peripheral neuropathy (DPN) is a disabling common complication of diabetes mellitus (DM). Thrombin, a coagulation factor, is increased in DM and affects nerve function via its G-protein coupled protease activated receptor 1 (PAR1). Methods: A novel PAR1 modulator (PARIN5) was designed based on the thrombin PAR1 recognition site. Coagulation, motor and sensory function and small fiber loss were evaluated by employing the murine streptozotocin diabetes model. Results: PARIN5 showed a safe coagulation profile and showed no significant effect on weight or glucose levels. Diabetic mice spent shorter time on the rotarod (p < 0.001), and had hypoalgesia (p < 0.05), slow conduction velocity (p < 0.0001) and reduced skin innervation (p < 0.0001). Treatment with PARIN5 significantly improved rotarod performance (p < 0.05), normalized hypoalgesia (p < 0.05), attenuated slowing of nerve conduction velocity (p < 0.05) and improved skin innervation (p < 0.0001). Conclusion: PARIN5 is a novel pharmacological approach for prevention of DPN development, via PAR1 pathway modulation.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::85d2995b115be7ad66694c46e4202a1d http://europepmc.org/articles/PMC7698286 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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